This program is designed to define the pathophysiology and to formulate methods of management of the two principal complications of vascular grafting: infection and thrombosis; and to reduce the incidence of these complications by identifying those aspects of graft design and material that are experimentally associated with a reduced susceptibility to bacteremic infection or thrombosis. Data from our previous studies indicate that transient bacteremia is a potential mechanism for infection in prosthetic arterial grafts; that the incidence of infectibility is reduced with healing time; and that the specific aspect of healing that provides protection against bacteremic infection is the development of a complete pseudointima. Pilot studies suggest that variability of the healing time/infectibility relationship exists among prosthetic grafts of differing design and material. A series of experiments are designed to identify these differences, the graft material and methods of fabrication that provide the most rapid and complete healing, and the lowest susceptibility to graft infection due to bacteremic challenge. The project also aims to develop alternative materials for arterial reconstruction in the presence of infection or wound contamination. Our earlier data indicate that fresh autogenous artery and vein, as well as fresh allograft artery, will heal and function when implanted in an infected wound. We plan to evaluate the use of cryopreservation as a method of providing conveniently available fresh, live allograft materials for implantation in infected or contaminated fields. Our final area of interest is the determination of the fabrication and composition of arterial grafting materials 4mm and less in diameter, which can be used for arterial implantation and have both a low rate of thrombosis and a low susceptibility to bacteremic infection. Methods for evaluation of arterial segments under study include an analysis of endothelial fibrinolytic activator activity, standard microscopic and scanning electron microscopic analysis of the graft surface and wall, and of long term patency.